Hong S.-Y,
Radosevich AT.
*
Massachusetts Institute of Technology, Cambridge, USA
Chemoselective Primary Amination of Aryl Boronic Acids by P
III/P
V=O Catalysis: Synthetic Capture of the Transient Nef Intermediate HNO.
J. Am. Chem. Soc. 2022;
144: 8902-8907
DOI:
10.1021/jacs.2c02922
Key words
Nef decomposition - arylboronic acids - phosphetane-catalyst - late-stage functionalization
Significance
Primary amination of aryl nucleophiles represents a valuable transformation though
is limited to some degree by the documented safety concerns and/or availability of
suitable H2N+ synthons. The current report exploits the Nef decomposition of 2-nitropropane (2) to form in situ the nitroxyl intermediate HNO, which is captured by a phosphetane-based
catalyst generating an oxazaphosphirane that reacts with the boronic acid to provide
the desired C–N coupled product through ring opening followed by a 1,2-metalate rearrangement.
Comment
Model studies demonstrated that not only was judicious selection of the catalyst and
solvent important for the optimal outcome of the reaction but inclusion of HMDS as
an additive significantly enhanced the yield through base-promoted activation of 2-nitropropane.
The methodology was shown to be relatively insensitive to both the electronic and
steric constraints of the substrates and was demonstrated for a range of heterocyclic
boronic acids including N-basic heterocyclic systems (7–9) that would be incompatible with electrophilic NH2-aminating reagents. The new protocol was shown to be complementary in scope and chemoselectivity
to transition-metal-catalyzed methods of aryl amination and was further applied for
the late-stage functionalization of drug-like molecules (10–12).
